Severe hypocalcemia with atypical symptoms after zoledronic acid in palliative care: a deprescribing pitfall

Severe hypocalcemia with atypical symptoms after zoledronic acid in palliative care: a deprescribing pitfall | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Severe hypocalcemia with atypical symptoms after zoledronic acid in palliative care: a deprescribing pitfall Till Arnold, Jennifer Berner-Sharma, Daniela Rudolph, Claudia Bausewein, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8661643/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Mar, 2026 Read the published version in BMC Palliative Care → Version 1 posted 10 You are reading this latest preprint version Abstract Background Symptomatic hypocalcemia is uncommon in palliative care and may therefore be overlooked. While deprescribing is a key principle in this setting, routine discontinuation of calcium and vitamin D supplementation may be harmful in selected high-risk patients, particularly after recent antiresorptive therapy. Case presentation: A 74-year-old woman with hormone receptor-positive metastatic breast cancer, extensive bone metastases, chronic kidney disease, was admitted to a German palliative care unit. Four weeks prior, she had received zoledronic acid, and calcium and vitamin D supplementation were discontinued on admission. She subsequently developed persistent nausea, vomiting and bronchospasm without classical neuromuscular signs, which were initially attributed to other causes. At a corrected calcium nadir of 0.95 mmol/L intravenous calcium was started and symptoms resolved. Oral intake resumed and supplementation was restarted. She was discharged to hospice care and died nine months later. Conclusion After recent antiresorptive therapy, especially in patients with additional risk factors such as renal impairment, hypocalcemia may present with atypical symptoms including nausea or bronchospasm. This case highlights a potential pitfall of deprescribing in palliative care and underscores the need for individualized decisions regarding calcium and vitamin D supplementation to prevent delayed diagnosis and avoidable symptom burden. hypocalcemia nausea bronchospasm palliative palliative care deprescribing Background Symptomatic hypocalcemia is uncommon in palliative care and may therefore be overlooked. While deprescribing is an important principle in a palliative care setting (1), discontinuation of long-term supplements such as calcium and vitamin D may be harmful in selected high-risk situations. We report a case of severe hypocalcemia following recent zoledronic acid administration and discontinuation of calcium/vitamin D, presenting with atypical symptoms including bronchospasm and nausea in the absence of classical neuromuscular signs. This case highlights an underrecognized presentation of hypocalcemia and its implications for deprescribing decisions in palliative care. Case presentation A 74-year-old woman with hormone receptor-positive metastatic breast cancer with extensive bone metastases and prior skeletal complications (spinal involvement, pathologic fracture) and palliative radiotherapy was admitted to a German inpatient palliative care unit in a tertiary hospital for symptom control and care planning. The patient had declined systemic cancer therapy multiple times in the past. One month prior to admission, she consented to letrozole and zoledronic acid therapy to reduce bone-related events. Her extended medical history included atrial fibrillation, hypertension, hypothyroidism, and unilateral renal atrophy. On admission, symptoms included pain, dry mouth, mild dyspnea, generalized weakness, and poor mobility (Australian-modified Karnofsky Performance Status 30%). Labs showed CKD, mild hypocalcemia, pancytopenia and mildly elevated CRP (Table 1 ). Pre-admission oral medications included calcium 1000mg OD, vitamin D 1000 IU OD, pantoprazole 40 mg OD, torasemide 10 mg BD, xipamide 10 mg OD among other drugs. In line with the patient's wishes, calcium/vitamin D and other non-essential drugs were discontinued. Diuretics were continued, pain control was optimized with a rotation from tilidin/naloxone to transdermal buprenorphine 15 µg/h, leading to overall clinical stabilization. A symptomatic catheter-associated urinary tract infection 4 days after admission was treated empirically with ciprofloxacin and the catheter was replaced. The following day, the patient started to develop nausea and vomiting. Despite switching antibiotics to cotimoxazole and symptomatic treatment with metoclopramide, nausea and vomiting persisted. Positional vertigo was considered, and hydromorphone was administered prior to positional testing due to mobilization pain. Shortly thereafter, the patient developed dyspnea with inspiratory stridor, somnolence, and worsening nausea, with oxygen saturation falling below 80% on room air. No allergic, infectious or opioid intoxication signs were found. ECG revealed QTc prolongation of 480 ms. Point-of-care ultrasound showed no pleural effusion or pneumothorax and no signs suggestive of right heart strain. Labs revealed worsening renal function and a marked drop in albumin-corrected calcium (Table 1 , day 7). Our initial clinical suspicion focused on early aspiration pneumonia, and symptomatic treatment was initiated: to treat the bronchospasm, we prescribed salbutamol and ipratropium bromide TD by inhalation and dexamethasone 4 mg IV OD over 3 days. For nausea relief, metoclopramide 5 mg was administered TD. However, over the next two days, symptoms worsened, oral intake became impossible, and signs of terminal decline emerged. Further laboratory testing on day 9 ruled out infection but revealed severe hypocalcemia (0.95 mmol/L), hyperphosphatemia, mildly elevated magnesium, normal 25-OH-vitamin D, hyponatremia and worsening of kidney function (Table 1 ). Despite the absence of tetany or paresthesias, a therapeutic trial with intravenous calcium gluconate was initiated. First, potassium 40 mval in 1000 mL crystalloid solution was replaced, then two intravenous boluses of each 10 mL calcium gluconate 10% in 50 mL NaCl 0.9% over 1 hour, followed by a continuous infusion of 100 mL calcium gluconate 10% in 1000 mL NaCl 0.9% over 24 hours were administered. Shortly after initiating the infusion, the patient developed palpitations and new-onset atrial fibrillation, which was managed successfully with 5 mg intravenous metoprolol. As corrected calcium rose, dyspnea and nausea improved and oral intake resumed; oral calcium/vitamin D was restarted. Parathyroid hormone (PTH) was elevated to 162 pg/mL, suggesting secondary hyperparathyroidism due to functional calcium deficiency. The patient was discharged in stable condition to hospice care. The patient died nine months later. Table 1 Laboratory values on admission and during the trajectory Patient values on admission Day 7 Day 9 Day 10 Day 11 Day 13 Day 15 Reference range Creatinine 1.1 1.3 1.5 1.5 1.1 0.9 0.8 0.5–1.0 mg/dL GFR 49 40 34 34 49 63 73 ≥ 60 mL/min/1.73m² Calcium 1.89 1.17 1.00 1.15 1.29 1.60 1.62 2.05–2.65 mmol/L Albumin 3.8 3.8 4.2 3.7 3.7 3.8 3.5–5.2 g/dL Albumin-corrected Calcium 1.94 1.22 0.95 1.37 1.68 1.67 2.05–2.65 mmol/L Sodium 137 133 136 134 139 138 140 135–145 mmol/L Potassium 3.9 3.0 3.3 4.1 3.4 3.7 4.2 3.5–5.1 mmol/L CRP 0.7 1.7 1.0 0.7 0.6 ≤ 0.5 mg/dL Magnesium 1.06 1.11 1.19 1.24 0.66–1.07 mmol/L PTH 162 15–65 pg/mL 25-OH-Vitamin D 38.2 20–100 ng/mL Inorganic phosphate 8.2 4.9 2.5–4.8 mg/dL Alkaline phosphatase 316 35–105 U/L LDH 392 517 517 457 ≤ 249 U/L Leukocytes 3.04 3.79 5.74 5.86 5.15 4.00–10.40 G/L Hemoglobin 8.6 8.7 9.5 8.1 9.3 11.5–15.4 g/dL Thrombocytes 143 186 241 229 217 176–391 G/L Discussion and conclusion Pathogenesis and epidemiology of hypocalcemia Serum calcium homeostasis is regulated primarily by parathyroid hormone (PTH), vitamin D, calcium ions themselves, and phosphate. Hypocalcemia most commonly results from disturbances in PTH secretion or vitamin D metabolism (2), but may also occur due to renal failure, hyperphosphatemia, osteoblastic bone metastases, or severe systemic illness (3, 4). Approximately 40–45% of circulating calcium is protein-bound, predominantly to albumin, while only the ionized fraction is biologically active (5). In patients with hypoalbuminemia, albumin-corrected or ionized calcium should therefore be assessed to avoid pseudohypocalcemia (2, 6). We were unable to identify any literature on the incidence or prevalence of clinically relevant hypocalcemia in palliative care settings. In cancer patients receiving bone-modifying agents (BMA) such as bisphosphonates or denosumab, hypocalcemia is a recognized adverse effect, with reported incidences ranging from 6% to 35% (7–9), and severe cases occurring in up to 9% (8). Table 2 sums identified risk factors for the development of hypocalcemia in patients receiving BMA. Also other medications can cause hypocalcemia, including calcium binders such as citrate, bisphosphonates, denosumab, cinacalcet, foscarnet, fluoride intoxication, chemotherapeutic agents such as cisplatin, or immune checkpoint inhibitors like nivolumab (10–17). Table 2 Risk factors of hypocalcemia related to bone-modifying agents Category Risk factor Study and medication Patient/disease related Low pretreatment vitamin D Denosumab, zoledronic acid (8) Low pretreatment calcium Denosumab (9, 13) Renal impairment Denosumab (13), zoledronic acid (7) Hematologic malignancy and/or bone metastases Denosumab, zoledronic acid (8) Elevated alkaline phosphatase Denosumab (9, 18) Age ≥ 65, male sex Denosumab (9, 13) Low haemoglobin Denosumab (18) Therapy related Concomitant use of dexamethason or vonoprazan Denosumab (18) Concomitant use of loop diuretics, aminoglycosides, calcitonin Zoledronic acid (19) Co-administration of cytotoxic agents Denosumab (9) Electrolyte/metabolic Hypomagnesaemia Denosumab (13), zoledronic acid (7) Hypophosphatemia Denosumab (13) Symptoms and diagnosis of hypocalcemia Hypocalcemia may be asymptomatic or present with a wide range of clinical manifestations, depending on severity and acuity. Acute hypocalcemia typically causes neuromuscular irritability and cardiovascular symptoms. A number of clinical signs (e.g., Trousseau or Chvostek) indicate this excitability (20–22). Less common symptoms such as bronchospasm (23), psychiatric manifestations (24) have also been reported. Table 3 shows clinical findings in hypocalcemia (17, 20–27). Gastrointestinal symptoms are rarely emphasized in the literature. Nausea has only sporadically been described as a manifestation of hypocalcemia (17); however, in our case it was the leading symptom and resolved promptly after calcium replacement, suggesting a causal relationship. We thereofore believe it should be included among atypical symptoms of hypocalcemia. Diagnosis relies on laboratory assessment of albumin-corrected or ionized calcium, with additional evaluation of PTH, vitamin D, phosphate, magnesium, and renal function to clarify the underlying mechanism (28). Table 3 Symptoms of acute and chronic hypocalcemia Acute hypocalcemia Neuromuscular irritability Paresthesias (perioral and extremities) Muscle twitching, cramps and weakness Carpopedal spasm Tetany Seizures (focal, petit mal, grand mal) Laryngospasm Bronchospasm Cardiac Prolongation of QTc interval Hypotension Heart failure Arrhythmia Neuropsychiatric Confusion Anxiety Agitation Ocular Papilledema Gastrointestinal Nausea Vomiting Abdominal pain Chronic hypocalcemia Neurologic Basal ganglia calcifications / Extrapyramidal disorders (Fahr disease) Cognitive decline / dementia Ocular Subcapsular cataracts Papilledema Optic neuritis Ectodermal / dental Alopecia Xeroderma Brittle nails, dry skin Enamel hypoplasia / altered tooth morphology Management of hypocalcemia Management of hypocalcemia depends on symptom severity, acuity, and underlying cause. Acute symptomatic hypocalcemia typically requires intravenous calcium administration under inpatient monitoring (29), whereas chronic or asymptomatic cases may be managed with oral supplementation (30). Intravenous therapy is typically administered as repeated boluses followed by continuous infusion if needed, aiming to restore calcium levels to the low-normal range (22). Oral calcium and vitamin D supplementation should be initiated as soon as clinically feasible. Potential complications of intravenous calcium include arrhythmias, especially after rapid administration, local vein irritation (in solutions with more than 200 mg/100 mL of elemental calcium), and tissue calcification may result from extravasation (31). Compensating for any hypomagnesemia to overcome possible PTH resistance needs to be considered [28]. Synopsis and relevance in palliative care This case highlights an important pitfall of deprescribing in palliative care: while discontinuation of non-essential medications is a key principle (1), routine cessation of supplements such as calcium and vitamin D may be harmful in selected high-risk situations (Table 2 ). In our patient, recent zoledronic acid therapy, pre-existing renal impairment, and low baseline calcium levels constituted a constellation in which continued supplementation was clinically relevant. The decision to deprescribe calcium/vitamin D was made in accordance with the patient’s wishes and common palliative practice, yet the potential delayed effects of antiresorptive therapy were underestimated. This illustrates how the benefits and risks of deprescribing may shift after specific oncological treatments, even when these treatments were administered weeks earlier (32). Hypocalcemia may be particularly difficult to recognize in palliative care, where symptoms are often multifactorial and laboratory monitoring may be limited. In this context, atypical manifestations such as nausea or bronchospasm can easily be misattributed to disease progression, infection, medication side effects, or terminal decline. Failure to recognize hypocalcemia may lead to unnecessary interventions and delayed symptom relief, and inappropriate therapeutic descisions that may even exacerbate the underlying problem, such as the administration of dexamethasone. Our case underscores the need for individualized deprescribing decisions rather than blanket discontinuation of supplements. In patients with recent exposure to bisphosphonates or denosumab, especially those with additional risk factors, calcium and vitamin D supplementation should generally be continued if oral intake is preserved and prognosis allows. In oncologic patients receiving BMA, it is even recommended to check calcium levels before each dose and two weeks after the first dose for patients with risk factors (19, 32). Awareness of this potential complication may help prevent avoidable suffering and misinterpretation of symptoms in palliative care settings. Home and hospice care perspective In Germany, specialist palliative home care (spezialisierte ambulante Palliativversorgung, SAPV) has become an important pillar of palliative care for patients wishing to stay at home (33), other patients stay in hospices at the end of their lives. In these settings, hypocalcemia may be easily overlooked, particularly if symptoms are atypical such as nausea or bronchospasm. If a patient on antiresorptive therapy develops new or unexplained symptoms, serum calcium should be checked if feasible. Oral calcium and vitamin D supplementation can be safely managed at home. If intravenous calcium is necessary and indicated, referral to hospital or a specialized palliative care unit remains the safest approach. Only in carefully selected situations, with a confirmed diagnosis and explicit patient consent, could intravenous therapy be considered at home when hospital admission is not an option. Our case underlines the importance of such vigilance: early recognition and appropriate management of hypocalcemia, even when presenting with atypical symptoms such as nausea, may prevent misdiagnosis and unnecessary interventions in both inpatient and palliative home care. Abbreviations BD – Twice daily BMA – Bone modifying agent(s) CKD – Chronic kidney disease CRP – C-reactive protein ECG – Electrocardiogram GFR – Glomerular filtration rate IU – International units IV – Intravenous LDH – Lactate dehydrogenase OD – Once daily PTH – Parathyroid hormone QTc – Corrected QT interval SAPV – specialist palliative home care (Spezialisierte ambulante Palliativversorgung) TD – Three times daily Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent for publication was obtained from the patient’s next of kin. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Competing interests The authors declare that they have no competing interests Funding No funding was received. Authors’ contributions TA initiated and wrote the manuscript, and obtained the consent for publication. JBS corrected and edited the manuscript. DR researchend the tables’ contend and built the tables. CB corrected and edited the manuscript. CR contributed to writing parts of the discussion, corrected and edited the manuscript. Declaration of generative AI in scientific writing During the preparation of this work the authors used ChatGPT (OpenAI) in order to identify and correct grammatical, semantic and stylistic errors in the text. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. Acknowledgements Not applicable. References Curtin D, Gallagher P, O'Mahony D. Deprescribing in older people approaching end-of-life: development and validation of STOPPFrail version 2. Age Ageing. 2021;50(2):465-71. Riccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol. 2010;298(3):F485-99. Smallridge RC, Wray HL, Schaaf M. 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Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis. Sci Rep. 2021;11(1):978. Fachinformation, Zometa® 4 mg/5 ml, Konzentrat zur Herstellung einer Infusionslösung. 03/2006. Macefield G, Burke D. Paraesthesiae and tetany induced by voluntary hyperventilation. Increased excitability of human cutaneous and motor axons. Brain. 1991;114 ( Pt 1B):527-40. Bilezikian JP. Hypoparathyroidism. J Clin Endocrinol Metab. 2020;105(6):1722-36. Schafer AL SD. Hypocalcemia: Diagnosis and Treatment. In: Feingold KR AS, Anawalt B, et al., editor. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-; 2016. Kumari A, Nangrani K, Dolkar T, Arora A, Schmidt M. Hypocalcemia Induced Bronchospasm. Cureus. 2022;14(6):e26339. Lin KF, Chen KH, Huang WL. Organic anxiety in a woman with breast cancer receiving denosumab. Gen Hosp Psychiatry. 2015;37(2):192.e7-8. Wong CK, Lau CP, Cheng CH, Leung WH, Freedman B. Hypocalcemic myocardial dysfunction: short- and long-term improvement with calcium replacement. Am Heart J. 1990;120(2):381-6. Bajandas FJ, Smith JL. Optic nueritis in hypoparathyroidism. Neurology. 1976;26(5):451-4. Rajendram R, Deane JA, Barnes M, Swift PG, Adamson K, Pearce S, et al. Rapid onset childhood cataracts leading to the diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Am J Ophthalmol. 2003;136(5):951-2. Hannan FM, Thakker RV. Investigating hypocalcaemia. Bmj. 2013;346:f2213. Schafer AL SD. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Rosen CJ, editor. South Dartmouth (MA): John Wiley and Sons; 2013. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008;359(4):391-403. Tohme JF, Bilezikian JP. Diagnosis and Treatment of Hypocalcemic Emergencies. The Endocrinologist. 1996;6(1). Fachinformation, XGEVA® 120mg Injektionslösung. 2025/07. Appelmann I, Hoffmann-Menzel H. [Specialized outpatient palliative care (SAPV) : Basics, indications and prescription in clinical practice]. Schmerz. 2022;36(5):371-80. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8661643","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":581337333,"identity":"58b3d327-b652-4202-9921-d85e111ae3a3","order_by":0,"name":"Till Arnold","email":"data:image/png;base64,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","orcid":"","institution":"LMU Klinikum","correspondingAuthor":true,"prefix":"","firstName":"Till","middleName":"","lastName":"Arnold","suffix":""},{"id":581337334,"identity":"5376855d-2427-47b9-ac9b-49ea164b6c1d","order_by":1,"name":"Jennifer Berner-Sharma","email":"","orcid":"","institution":"LMU Klinikum","correspondingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"","lastName":"Berner-Sharma","suffix":""},{"id":581337335,"identity":"aeb23dd3-9961-4689-bb0e-e4a2065fe482","order_by":2,"name":"Daniela Rudolph","email":"","orcid":"","institution":"LMU Klinikum","correspondingAuthor":false,"prefix":"","firstName":"Daniela","middleName":"","lastName":"Rudolph","suffix":""},{"id":581337336,"identity":"e497a6ce-6cb7-4bf8-93f6-ae0bcbce8360","order_by":3,"name":"Claudia Bausewein","email":"","orcid":"","institution":"LMU Klinikum","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"","lastName":"Bausewein","suffix":""},{"id":581337337,"identity":"b6155bce-3d03-46a5-ba1b-b959f1de042d","order_by":4,"name":"Constanze Rémi","email":"","orcid":"","institution":"LMU Klinikum","correspondingAuthor":false,"prefix":"","firstName":"Constanze","middleName":"","lastName":"Rémi","suffix":""}],"badges":[],"createdAt":"2026-01-21 15:39:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8661643/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8661643/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12904-026-02070-8","type":"published","date":"2026-03-21T15:58:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":105223327,"identity":"921136d6-0ec5-4969-8ec9-ebf9eda30f73","added_by":"auto","created_at":"2026-03-23 16:03:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":806119,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8661643/v1/0704c39a-7047-4970-9391-c7c7d866f975.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Severe hypocalcemia with atypical symptoms after zoledronic acid in palliative care: a deprescribing pitfall","fulltext":[{"header":"Background","content":"\u003cp\u003eSymptomatic hypocalcemia is uncommon in palliative care and may therefore be overlooked. While deprescribing is an important principle in a palliative care setting (1), discontinuation of long-term supplements such as calcium and vitamin D may be harmful in selected high-risk situations. We report a case of severe hypocalcemia following recent zoledronic acid administration and discontinuation of calcium/vitamin D, presenting with atypical symptoms including bronchospasm and nausea in the absence of classical neuromuscular signs. This case highlights an underrecognized presentation of hypocalcemia and its implications for deprescribing decisions in palliative care.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 74-year-old woman with hormone receptor-positive metastatic breast cancer with extensive bone metastases and prior skeletal complications (spinal involvement, pathologic fracture) and palliative radiotherapy was admitted to a German inpatient palliative care unit in a tertiary hospital for symptom control and care planning. The patient had declined systemic cancer therapy multiple times in the past. One month prior to admission, she consented to letrozole and zoledronic acid therapy to reduce bone-related events. Her extended medical history included atrial fibrillation, hypertension, hypothyroidism, and unilateral renal atrophy.\u003c/p\u003e \u003cp\u003eOn admission, symptoms included pain, dry mouth, mild dyspnea, generalized weakness, and poor mobility (Australian-modified Karnofsky Performance Status 30%). Labs showed CKD, mild hypocalcemia, pancytopenia and mildly elevated CRP (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePre-admission oral medications included calcium 1000mg OD, vitamin D 1000 IU OD, pantoprazole 40 mg OD, torasemide 10 mg BD, xipamide 10 mg OD among other drugs. In line with the patient's wishes, calcium/vitamin D and other non-essential drugs were discontinued. Diuretics were continued, pain control was optimized with a rotation from tilidin/naloxone to transdermal buprenorphine 15 µg/h, leading to overall clinical stabilization. A symptomatic catheter-associated urinary tract infection 4 days after admission was treated empirically with ciprofloxacin and the catheter was replaced. The following day, the patient started to develop nausea and vomiting. Despite switching antibiotics to cotimoxazole and symptomatic treatment with metoclopramide, nausea and vomiting persisted. Positional vertigo was considered, and hydromorphone was administered prior to positional testing due to mobilization pain. Shortly thereafter, the patient developed dyspnea with inspiratory stridor, somnolence, and worsening nausea, with oxygen saturation falling below 80% on room air. No allergic, infectious or opioid intoxication signs were found. ECG revealed QTc prolongation of 480 ms. Point-of-care ultrasound showed no pleural effusion or pneumothorax and no signs suggestive of right heart strain. Labs revealed worsening renal function and a marked drop in albumin-corrected calcium (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, day 7). Our initial clinical suspicion focused on early aspiration pneumonia, and symptomatic treatment was initiated: to treat the bronchospasm, we prescribed salbutamol and ipratropium bromide TD by inhalation and dexamethasone 4 mg IV OD over 3 days. For nausea relief, metoclopramide 5 mg was administered TD. However, over the next two days, symptoms worsened, oral intake became impossible, and signs of terminal decline emerged. Further laboratory testing on day 9 ruled out infection but revealed severe hypocalcemia (0.95 mmol/L), hyperphosphatemia, mildly elevated magnesium, normal 25-OH-vitamin D, hyponatremia and worsening of kidney function (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Despite the absence of tetany or paresthesias, a therapeutic trial with intravenous calcium gluconate was initiated. First, potassium 40 mval in 1000 mL crystalloid solution was replaced, then two intravenous boluses of each 10 mL calcium gluconate 10% in 50 mL NaCl 0.9% over 1 hour, followed by a continuous infusion of 100 mL calcium gluconate 10% in 1000 mL NaCl 0.9% over 24 hours were administered. Shortly after initiating the infusion, the patient developed palpitations and new-onset atrial fibrillation, which was managed successfully with 5 mg intravenous metoprolol. As corrected calcium rose, dyspnea and nausea improved and oral intake resumed; oral calcium/vitamin D was restarted. Parathyroid hormone (PTH) was elevated to 162 pg/mL, suggesting secondary hyperparathyroidism due to functional calcium deficiency. The patient was discharged in stable condition to hospice care. The patient died nine months later.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory values on admission and during the trajectory\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient values on admission\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDay 7\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDay 9\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDay 10\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDay 11\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDay 13\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDay 15\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eReference range\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCreatinine\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.5–1.0 mg/dL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGFR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e≥ 60 mL/min/1.73m²\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCalcium\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.89\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.17\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.15\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.29\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.60\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.62\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.05–2.65 mmol/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlbumin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.5–5.2 g/dL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlbumin-corrected Calcium\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.94\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.22\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.37\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.68\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.67\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.05–2.65 mmol/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSodium\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e139\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e140\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e135–145 mmol/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePotassium\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.5–5.1 mmol/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e≤ 0.5 mg/dL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMagnesium\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.11\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.19\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.24\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.66–1.07 mmol/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePTH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e162\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e15–65 pg/mL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e25-OH-Vitamin D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20–100 ng/mL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInorganic phosphate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.5–4.8 mg/dL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlkaline phosphatase\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e316\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35–105 U/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDH\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e392\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e517\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e517\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e457\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e≤ 249 U/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLeukocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.04\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.79\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.74\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.86\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.15\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.00–10.40 G/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHemoglobin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.3\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11.5–15.4 g/dL\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThrombocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e186\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e241\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e229\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e217\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e176–391 G/L\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e \u003cp\u003e\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion and conclusion","content":"\u003ch2\u003ePathogenesis and epidemiology of hypocalcemia\u003c/h2\u003e\u003cp\u003eSerum calcium homeostasis is regulated primarily by parathyroid hormone (PTH), vitamin D, calcium ions themselves, and phosphate. Hypocalcemia most commonly results from disturbances in PTH secretion or vitamin D metabolism (2), but may also occur due to renal failure, hyperphosphatemia, osteoblastic bone metastases, or severe systemic illness (3, 4). Approximately 40–45% of circulating calcium is protein-bound, predominantly to albumin, while only the ionized fraction is biologically active (5). In patients with hypoalbuminemia, albumin-corrected or ionized calcium should therefore be assessed to avoid pseudohypocalcemia (2, 6).\u003c/p\u003e\u003cp\u003eWe were unable to identify any literature on the incidence or prevalence of clinically relevant hypocalcemia in palliative care settings. In cancer patients receiving bone-modifying agents (BMA) such as bisphosphonates or denosumab, hypocalcemia is a recognized adverse effect, with reported incidences ranging from 6% to 35% (7–9), and severe cases occurring in up to 9% (8). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e sums identified risk factors for the development of hypocalcemia in patients receiving BMA.\u003c/p\u003e\u003cp\u003eAlso other medications can cause hypocalcemia, including calcium binders such as citrate, bisphosphonates, denosumab, cinacalcet, foscarnet, fluoride intoxication, chemotherapeutic agents such as cisplatin, or immune checkpoint inhibitors like nivolumab (10–17).\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors of hypocalcemia related to bone-modifying agents\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRisk factor\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStudy and medication\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003ePatient/disease related\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow pretreatment vitamin D\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab, zoledronic acid (8)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow pretreatment calcium\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (9, 13)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRenal impairment\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (13), zoledronic acid (7)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHematologic malignancy and/or bone metastases\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab, zoledronic acid (8)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eElevated alkaline phosphatase\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (9, 18)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge ≥ 65, male sex\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (9, 13)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow haemoglobin\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (18)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eTherapy related\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConcomitant use of dexamethason or vonoprazan\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (18)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConcomitant use of loop diuretics, aminoglycosides, calcitonin\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eZoledronic acid (19)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCo-administration of cytotoxic agents\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (9)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eElectrolyte/metabolic\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypomagnesaemia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (13), zoledronic acid (7)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypophosphatemia\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDenosumab (13)\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\n\u003ch3\u003eSymptoms and diagnosis of hypocalcemia\u003c/h3\u003e\n\u003cp\u003eHypocalcemia may be asymptomatic or present with a wide range of clinical manifestations, depending on severity and acuity. Acute hypocalcemia typically causes neuromuscular irritability and cardiovascular symptoms. A number of clinical signs (e.g., Trousseau or Chvostek) indicate this excitability (20\u0026ndash;22). Less common symptoms such as bronchospasm (23), psychiatric manifestations (24) have also been reported. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows clinical findings in hypocalcemia (17, 20\u0026ndash;27).\u003c/p\u003e \u003cp\u003eGastrointestinal symptoms are rarely emphasized in the literature. Nausea has only sporadically been described as a manifestation of hypocalcemia (17); however, in our case it was the leading symptom and resolved promptly after calcium replacement, suggesting a causal relationship. We thereofore believe it should be included among atypical symptoms of hypocalcemia.\u003c/p\u003e \u003cp\u003eDiagnosis relies on laboratory assessment of albumin-corrected or ionized calcium, with additional evaluation of PTH, vitamin D, phosphate, magnesium, and renal function to clarify the underlying mechanism (28).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSymptoms of acute and chronic hypocalcemia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAcute hypocalcemia\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeuromuscular irritability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParesthesias (perioral and extremities)\u003c/p\u003e \u003cp\u003eMuscle twitching, cramps and weakness\u003c/p\u003e \u003cp\u003eCarpopedal spasm\u003c/p\u003e \u003cp\u003eTetany\u003c/p\u003e \u003cp\u003eSeizures (focal, petit mal, grand mal)\u003c/p\u003e \u003cp\u003eLaryngospasm\u003c/p\u003e \u003cp\u003eBronchospasm\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eProlongation of QTc interval\u003c/p\u003e \u003cp\u003eHypotension\u003c/p\u003e \u003cp\u003eHeart failure\u003c/p\u003e \u003cp\u003eArrhythmia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeuropsychiatric\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConfusion\u003c/p\u003e \u003cp\u003eAnxiety\u003c/p\u003e \u003cp\u003eAgitation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePapilledema\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003cp\u003eAbdominal pain\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChronic hypocalcemia\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurologic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBasal ganglia calcifications / Extrapyramidal disorders (Fahr disease)\u003c/p\u003e \u003cp\u003eCognitive decline / dementia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubcapsular cataracts\u003c/p\u003e \u003cp\u003ePapilledema\u003c/p\u003e \u003cp\u003eOptic neuritis\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEctodermal / dental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAlopecia\u003c/p\u003e \u003cp\u003eXeroderma\u003c/p\u003e \u003cp\u003eBrittle nails, dry skin\u003c/p\u003e \u003cp\u003eEnamel hypoplasia / altered tooth morphology\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eManagement of hypocalcemia\u003c/h3\u003e\n\u003cp\u003eManagement of hypocalcemia depends on symptom severity, acuity, and underlying cause. Acute symptomatic hypocalcemia typically requires intravenous calcium administration under inpatient monitoring (29), whereas chronic or asymptomatic cases may be managed with oral supplementation (30). Intravenous therapy is typically administered as repeated boluses followed by continuous infusion if needed, aiming to restore calcium levels to the low-normal range (22). Oral calcium and vitamin D supplementation should be initiated as soon as clinically feasible.\u003c/p\u003e \u003cp\u003ePotential complications of intravenous calcium include arrhythmias, especially after rapid administration, local vein irritation (in solutions with more than 200 mg/100 mL of elemental calcium), and tissue calcification may result from extravasation (31). Compensating for any hypomagnesemia to overcome possible PTH resistance needs to be considered [28].\u003c/p\u003e\n\u003ch3\u003eSynopsis and relevance in palliative care\u003c/h3\u003e\n\u003cp\u003eThis case highlights an important pitfall of deprescribing in palliative care: while discontinuation of non-essential medications is a key principle (1), routine cessation of supplements such as calcium and vitamin D may be harmful in selected high-risk situations (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In our patient, recent zoledronic acid therapy, pre-existing renal impairment, and low baseline calcium levels constituted a constellation in which continued supplementation was clinically relevant.\u003c/p\u003e \u003cp\u003eThe decision to deprescribe calcium/vitamin D was made in accordance with the patient\u0026rsquo;s wishes and common palliative practice, yet the potential delayed effects of antiresorptive therapy were underestimated. This illustrates how the benefits and risks of deprescribing may shift after specific oncological treatments, even when these treatments were administered weeks earlier (32).\u003c/p\u003e \u003cp\u003eHypocalcemia may be particularly difficult to recognize in palliative care, where symptoms are often multifactorial and laboratory monitoring may be limited. In this context, atypical manifestations such as nausea or bronchospasm can easily be misattributed to disease progression, infection, medication side effects, or terminal decline. Failure to recognize hypocalcemia may lead to unnecessary interventions and delayed symptom relief, and inappropriate therapeutic descisions that may even exacerbate the underlying problem, such as the administration of dexamethasone.\u003c/p\u003e \u003cp\u003eOur case underscores the need for individualized deprescribing decisions rather than blanket discontinuation of supplements. In patients with recent exposure to bisphosphonates or denosumab, especially those with additional risk factors, calcium and vitamin D supplementation should generally be continued if oral intake is preserved and prognosis allows. In oncologic patients receiving BMA, it is even recommended to check calcium levels before each dose and two weeks after the first dose for patients with risk factors (19, 32). Awareness of this potential complication may help prevent avoidable suffering and misinterpretation of symptoms in palliative care settings.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eHome and hospice care perspective\u003c/h2\u003e \u003cp\u003eIn Germany, specialist palliative home care (spezialisierte ambulante Palliativversorgung, SAPV) has become an important pillar of palliative care for patients wishing to stay at home (33), other patients stay in hospices at the end of their lives. In these settings, hypocalcemia may be easily overlooked, particularly if symptoms are atypical such as nausea or bronchospasm. If a patient on antiresorptive therapy develops new or unexplained symptoms, serum calcium should be checked if feasible. Oral calcium and vitamin D supplementation can be safely managed at home. If intravenous calcium is necessary and indicated, referral to hospital or a specialized palliative care unit remains the safest approach. Only in carefully selected situations, with a confirmed diagnosis and explicit patient consent, could intravenous therapy be considered at home when hospital admission is not an option. Our case underlines the importance of such vigilance: early recognition and appropriate management of hypocalcemia, even when presenting with atypical symptoms such as nausea, may prevent misdiagnosis and unnecessary interventions in both inpatient and palliative home care.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBD \u0026ndash; Twice daily\u003c/p\u003e\n\u003cp\u003eBMA \u0026ndash; Bone modifying agent(s)\u003c/p\u003e\n\u003cp\u003eCKD \u0026ndash; Chronic kidney disease\u003c/p\u003e\n\u003cp\u003eCRP \u0026ndash; C-reactive protein\u003c/p\u003e\n\u003cp\u003eECG \u0026ndash; Electrocardiogram\u003c/p\u003e\n\u003cp\u003eGFR \u0026ndash; Glomerular filtration rate\u003c/p\u003e\n\u003cp\u003eIU \u0026ndash; International units\u003c/p\u003e\n\u003cp\u003eIV \u0026ndash; Intravenous\u003c/p\u003e\n\u003cp\u003eLDH \u0026ndash; Lactate dehydrogenase\u003c/p\u003e\n\u003cp\u003eOD \u0026ndash; Once daily\u003c/p\u003e\n\u003cp\u003ePTH \u0026ndash; Parathyroid hormone\u003c/p\u003e\n\u003cp\u003eQTc \u0026ndash; Corrected QT interval\u003c/p\u003e\n\u003cp\u003eSAPV \u0026ndash; specialist palliative home care \u003cem\u003e(Spezialisierte ambulante Palliativversorgung)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eTD \u0026ndash; Three times daily\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from the patient\u0026rsquo;s next of kin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTA initiated and wrote the manuscript, and obtained the consent for publication. JBS corrected and edited the manuscript. DR researchend the tables\u0026rsquo; contend and built the tables. CB corrected and edited the manuscript. CR contributed to writing parts of the discussion, corrected and edited the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of generative AI in scientific writing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this work the authors used ChatGPT (OpenAI) in order\u0026nbsp;to identify and correct grammatical, semantic and stylistic errors in the text. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCurtin D, Gallagher P, O\u0026apos;Mahony D. Deprescribing in older people approaching end-of-life: development and validation of STOPPFrail version 2. Age Ageing. 2021;50(2):465-71.\u003c/li\u003e\n\u003cli\u003eRiccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol. 2010;298(3):F485-99.\u003c/li\u003e\n\u003cli\u003eSmallridge RC, Wray HL, Schaaf M. Hypocalcemia with osteoblastic metastases in patient with prostate carcinoma. A cause of secondary hyperparathyroidism. Am J Med. 1981;71(1):184-8.\u003c/li\u003e\n\u003cli\u003eMurray RM, Grill V, Crinis N, Ho PW, Davison J, Pitt P. Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. J Clin Endocrinol Metab. 2001;86(9):4133-8.\u003c/li\u003e\n\u003cli\u003eBushinsky DA, Monk RD. Electrolyte quintet: Calcium. Lancet. 1998;352(9124):306-11.\u003c/li\u003e\n\u003cli\u003eVantour L GD. Primer on the metabolic bone diseases and disorders of mineral metabolism. 9 ed. Hoboken: Wiley-Blackwell; 2018. 1105 p.\u003c/li\u003e\n\u003cli\u003eChennuru S, Koduri J, Baumann MA. Risk factors for symptomatic hypocalcaemia complicating treatment with zoledronic acid. Intern Med J. 2008;38(8):635-7.\u003c/li\u003e\n\u003cli\u003eWhite PS, Dennis M, Jones EA, Weinberg JM, Sarosiek S. Risk Factors for Development of Hypocalcemia in Patients With Cancer Treated With Bone-Modifying Agents. J Natl Compr Canc Netw. 2020;18(4):420-7.\u003c/li\u003e\n\u003cli\u003eSaito Y, Takekuma Y, Komatsu Y, Sugawara M. Risk Analysis of Denosumab-Induced Hypocalcemia in Bone Metastasis Treatment: Renal Dysfunction Is Not a Risk Factor for Its Incidence in a Strict Denosumab Administration Management System with Calcium/Vitamin D Supplementation. Biol Pharm Bull. 2021;44(12):1819-23.\u003c/li\u003e\n\u003cli\u003eRutledge R, Sheldon GF, Collins ML. Massive transfusion. Crit Care Clin. 1986;2(4):791-805.\u003c/li\u003e\n\u003cli\u003eBolan CD, Cecco SA, Wesley RA, Horne M, Yau YY, Remaley AT, et al. Controlled study of citrate effects and response to i.v. calcium administration during allogeneic peripheral blood progenitor cell donation. Transfusion. 2002;42(7):935-46.\u003c/li\u003e\n\u003cli\u003eCairns CB, Niemann JT, Pelikan PC, Sharma J. Ionized hypocalcemia during prolonged cardiac arrest and closed-chest CPR in a canine model. Ann Emerg Med. 1991;20(11):1178-82.\u003c/li\u003e\n\u003cli\u003eSp\u0026aring;ngeus A, Rydetun J, Woisetschl\u0026auml;ger M. Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection. Osteoporos Int. 2024;35(1):173-80.\u003c/li\u003e\n\u003cli\u003eKido Y, Okamura T, Tomikawa M, Yamamoto M, Shiraishi M, Okada Y, et al. Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients with advanced colorectal or gastric carcinomas. Cancer. 1996;78(8):1794-7.\u003c/li\u003e\n\u003cli\u003eJacobson MA, Gambertoglio JG, Aweeka FT, Causey DM, Portale AA. Foscarnet-induced hypocalcemia and effects of foscarnet on calcium metabolism. J Clin Endocrinol Metab. 1991;72(5):1130-5.\u003c/li\u003e\n\u003cli\u003eGessner BD, Beller M, Middaugh JP, Whitford GM. Acute fluoride poisoning from a public water system. N Engl J Med. 1994;330(2):95-9.\u003c/li\u003e\n\u003cli\u003ePiranavan P, Li Y, Brown E, Kemp EH, Trivedi N. Immune Checkpoint Inhibitor-Induced Hypoparathyroidism Associated With Calcium-Sensing Receptor-Activating Autoantibodies. J Clin Endocrinol Metab. 2019;104(2):550-6.\u003c/li\u003e\n\u003cli\u003eKanbayashi Y, Sakaguchi K, Hongo F, Ishikawa T, Tabuchi Y, Ukimura O, et al. Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis. Sci Rep. 2021;11(1):978.\u003c/li\u003e\n\u003cli\u003eFachinformation, Zometa\u0026reg; 4 mg/5 ml, Konzentrat zur Herstellung einer Infusionsl\u0026ouml;sung. 03/2006.\u003c/li\u003e\n\u003cli\u003eMacefield G, Burke D. Paraesthesiae and tetany induced by voluntary hyperventilation. Increased excitability of human cutaneous and motor axons. Brain. 1991;114 ( Pt 1B):527-40.\u003c/li\u003e\n\u003cli\u003eBilezikian JP. Hypoparathyroidism. J Clin Endocrinol Metab. 2020;105(6):1722-36.\u003c/li\u003e\n\u003cli\u003eSchafer AL SD. Hypocalcemia: Diagnosis and Treatment. In: Feingold KR AS, Anawalt B, et al., editor. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-; 2016.\u003c/li\u003e\n\u003cli\u003eKumari A, Nangrani K, Dolkar T, Arora A, Schmidt M. Hypocalcemia Induced Bronchospasm. Cureus. 2022;14(6):e26339.\u003c/li\u003e\n\u003cli\u003eLin KF, Chen KH, Huang WL. Organic anxiety in a woman with breast cancer receiving denosumab. Gen Hosp Psychiatry. 2015;37(2):192.e7-8.\u003c/li\u003e\n\u003cli\u003eWong CK, Lau CP, Cheng CH, Leung WH, Freedman B. Hypocalcemic myocardial dysfunction: short- and long-term improvement with calcium replacement. Am Heart J. 1990;120(2):381-6.\u003c/li\u003e\n\u003cli\u003eBajandas FJ, Smith JL. Optic nueritis in hypoparathyroidism. Neurology. 1976;26(5):451-4.\u003c/li\u003e\n\u003cli\u003eRajendram R, Deane JA, Barnes M, Swift PG, Adamson K, Pearce S, et al. Rapid onset childhood cataracts leading to the diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Am J Ophthalmol. 2003;136(5):951-2.\u003c/li\u003e\n\u003cli\u003eHannan FM, Thakker RV. Investigating hypocalcaemia. Bmj. 2013;346:f2213.\u003c/li\u003e\n\u003cli\u003eSchafer AL SD. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Rosen CJ, editor. South Dartmouth (MA): John Wiley and Sons; 2013.\u003c/li\u003e\n\u003cli\u003eShoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008;359(4):391-403.\u003c/li\u003e\n\u003cli\u003eTohme JF, Bilezikian JP. Diagnosis and Treatment of Hypocalcemic Emergencies. The Endocrinologist. 1996;6(1).\u003c/li\u003e\n\u003cli\u003eFachinformation, XGEVA\u0026reg; 120mg Injektionsl\u0026ouml;sung. 2025/07.\u003c/li\u003e\n\u003cli\u003eAppelmann I, Hoffmann-Menzel H. [Specialized outpatient palliative care (SAPV) : Basics, indications and prescription in clinical practice]. Schmerz. 2022;36(5):371-80.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-palliative-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pcar","sideBox":"Learn more about [BMC Palliative Care](http://bmcpalliatcare.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pcar/default.aspx","title":"BMC Palliative Care","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"hypocalcemia, nausea, bronchospasm, palliative, palliative care, deprescribing","lastPublishedDoi":"10.21203/rs.3.rs-8661643/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8661643/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSymptomatic hypocalcemia is uncommon in palliative care and may therefore be overlooked. While deprescribing is a key principle in this setting, routine discontinuation of calcium and vitamin D supplementation may be harmful in selected high-risk patients, particularly after recent antiresorptive therapy.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 74-year-old woman with hormone receptor-positive metastatic breast cancer, extensive bone metastases, chronic kidney disease, was admitted to a German palliative care unit. Four weeks prior, she had received zoledronic acid, and calcium and vitamin D supplementation were discontinued on admission. She subsequently developed persistent nausea, vomiting and bronchospasm without classical neuromuscular signs, which were initially attributed to other causes. At a corrected calcium nadir of 0.95 mmol/L intravenous calcium was started and symptoms resolved. Oral intake resumed and supplementation was restarted. She was discharged to hospice care and died nine months later.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAfter recent antiresorptive therapy, especially in patients with additional risk factors such as renal impairment, hypocalcemia may present with atypical symptoms including nausea or bronchospasm. This case highlights a potential pitfall of deprescribing in palliative care and underscores the need for individualized decisions regarding calcium and vitamin D supplementation to prevent delayed diagnosis and avoidable symptom burden.\u003c/p\u003e","manuscriptTitle":"Severe hypocalcemia with atypical symptoms after zoledronic acid in palliative care: a deprescribing pitfall","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 11:40:44","doi":"10.21203/rs.3.rs-8661643/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-18T07:18:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-17T02:16:06+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-01T15:32:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70747105093483724449992657349301698602","date":"2026-02-01T09:50:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20570543858052277798296194522121313531","date":"2026-01-31T08:59:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-27T17:56:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-27T17:53:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-27T16:15:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-23T14:07:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Palliative Care","date":"2026-01-23T13:50:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-palliative-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pcar","sideBox":"Learn more about [BMC Palliative Care](http://bmcpalliatcare.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pcar/default.aspx","title":"BMC Palliative Care","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"35f39916-3c82-4160-9b71-62214621c3e4","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:01:04+00:00","versionOfRecord":{"articleIdentity":"rs-8661643","link":"https://doi.org/10.1186/s12904-026-02070-8","journal":{"identity":"bmc-palliative-care","isVorOnly":false,"title":"BMC Palliative Care"},"publishedOn":"2026-03-21 15:58:30","publishedOnDateReadable":"March 21st, 2026"},"versionCreatedAt":"2026-01-29 11:40:44","video":"","vorDoi":"10.1186/s12904-026-02070-8","vorDoiUrl":"https://doi.org/10.1186/s12904-026-02070-8","workflowStages":[]},"version":"v1","identity":"rs-8661643","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8661643","identity":"rs-8661643","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}